HTNV-induced upregulation of miR-146a in HUVECs promotes viral infection by modulating pro-inflammatory cytokine release

被引:18
作者
Chen, Qing-Zhou [1 ]
Luo, Fan [1 ]
Lu, Ming-Xiang [2 ]
Li, Ning [1 ]
Teng, Yan [1 ]
Huang, Qiu-Ling [1 ]
Zhu, Ni [3 ]
Wang, Guan-Yi [1 ]
Yue, Ming [4 ]
Zhang, Yun [5 ]
Feng, Yong [1 ]
Xiong, Hai-Rong [1 ]
Hou, Wei [1 ,3 ]
机构
[1] Wuhan Univ, State Key Lab Virol, Inst Med Virol, Hubei Prov Key Lab Allergy & Immunol,Sch Basic Me, 185 Donghu Rd, Wuhan 430071, Hubei, Peoples R China
[2] Wuhan Univ, Zhongnan Hosp, Ctr Gene Diag, 169 Donghu Rd, Wuhan 430071, Hubei, Peoples R China
[3] Hubei Univ Sci & Technol, Sch Basic Med, 88 Xianning Ave, Xianning 437100, Hubei, Peoples R China
[4] Nanjing Med Univ, Dept Infect Dis, Affiliated Hosp 1, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, Peoples R China
[5] Inst Mil Med Sci Nanjing Command, Nanjing 210002, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-146a; Pro-inflammatory cytokines; HTNV; NF-kappa B; NF-KAPPA-B; IMMUNE-RESPONSES; EXPRESSION; INTERFERON; MICRORNAS; INDUCTION; PROTEINS;
D O I
10.1016/j.bbrc.2017.08.073
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Increasing research has shown a link between viruses and miRNAs, such as miRNA-146a, in regulating virus infection and replication. In the current study, the association between miR-146a and hantaan virus (HTNV) infection in human umbilical vein endothelial cells (HUVECs) was investigated, with a focus on examining the expression of pro-inflammatory cytokines. The results showed that HTNV infection promoted the production of miR-146a in HUVECs and activated nuclear factor-kappa B (NF-kappa B) signaling, along with the upregulation of pro-inflammatory cytokines, including interleukin 8 (IL-8), C-C Motif Chemokine Ligand 5 (CCL5, also RANTES), interferon-inducible protein-10 (IP-10) and interferon beta (IFN-beta). Moreover, miR-146a exhibited a negative regulatory effect on the NF-kappa B pathway. Accordingly, a miR-146a inhibitor increased the expression of IL-8, CCL5, IP-10 and IFN-beta, whereas a miR-146a mimic reduced the levels of these cytokines. Consequently, exogenous transduction of miR-146a significantly enhanced HTNV replication in HUVEC cells. We also discovered that viral proteins (NP/GP) contributed to miR-146a expression via enhancement the activity of miR-146a promoter. In conclusion, these results imply the negative regulation of miR-146a on the production of HTNV-induced pro-inflammatory cytokines contributes to virus replication, which suggest that miR-146a may be regarded as a novel therapeutic target for HTNV infection. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:807 / 813
页数:7
相关论文
共 36 条
[1]   DENV Inhibits Type I IFN Production in Infected Cells by Cleaving Human STING [J].
Aguirre, Sebastian ;
Maestre, Ana M. ;
Pagni, Sarah ;
Patel, Jenish R. ;
Savage, Timothy ;
Gutman, Delia ;
Maringer, Kevin ;
Bernal-Rubio, Dabeiba ;
Shabman, Reed S. ;
Simon, Viviana ;
Rodriguez-Madoz, Juan R. ;
Mulder, Lubbertus C. F. ;
Barber, Glen N. ;
Fernandez-Sesma, Ana .
PLOS PATHOGENS, 2012, 8 (10)
[2]   Early Bunyavirus-Host Cell Interactions [J].
Albornoz, Amelina ;
Hoffmann, Anja B. ;
Lozach, Pierre-Yves ;
Tischler, Nicole D. .
VIRUSES-BASEL, 2016, 8 (05)
[3]   MicroRNAs: new regulators of immune cell development and function [J].
Baltimore, David ;
Boldin, Mark P. ;
O'Connell, Ryan M. ;
Rao, Dinesh S. ;
Taganov, Konstantin D. .
NATURE IMMUNOLOGY, 2008, 9 (08) :839-845
[4]   Hepatitis C Virus-Induced Upregulation of MicroRNA miR-146a-5p in Hepatocytes Promotes Viral Infection and Deregulates Metabolic Pathways Associated with Liver Disease Pathogenesis [J].
Bandiera, Simonetta ;
Pernot, Sophie ;
El Saghire, Hussein ;
Durand, Sarah C. ;
Thumann, Christine ;
Crouchet, Emilie ;
Ye, Tao ;
Fofana, Isabel ;
Oudot, Marine A. ;
Barths, Jochen ;
Schuster, Catherine ;
Pessaux, Patrick ;
Heim, Markus H. ;
Baumert, Thomas F. ;
Zeisel, Mirjam B. .
JOURNAL OF VIROLOGY, 2016, 90 (14) :6387-6400
[5]   Epstein-Barr virus latent membrane protein 1 induces cellular MicroRNA miR-146a, a modulator of lymphocyte signaling pathways [J].
Cameron, Jennifer E. ;
Yin, Qinyan ;
Fewell, Claire ;
Lacey, Michelle ;
McBride, Jane ;
Wang, Xia ;
Lin, Zhen ;
Schaefer, Brian C. ;
Flemington, Erik K. .
JOURNAL OF VIROLOGY, 2008, 82 (04) :1946-1958
[6]   UV-induced fragmentation of Cajal bodies [J].
Cioce, Mario ;
Boulon, Severine ;
Matera, A. Gregory ;
Lamond, Angus I. .
JOURNAL OF CELL BIOLOGY, 2006, 175 (03) :401-413
[7]   Discovery of hantavirus circulating among Rattus rattus in French Mayotte island, Indian Ocean [J].
Filippone, Claudia ;
Castel, Guillaume ;
Murri, Severine ;
Beaulieux, Frederik ;
Ermonval, Myriam ;
Jallet, Corinne ;
Wise, Emma L. ;
Ellis, Richard J. ;
Marston, Denise A. ;
McElhinney, Lorraine M. ;
Fooks, Anthony R. ;
Desvars, Amelie ;
Halos, Lenaig ;
Vourc'h, Gwenael ;
Marianneau, Philippe ;
Tordo, Noel .
JOURNAL OF GENERAL VIROLOGY, 2016, 97 :1060-1065
[8]   NF-κB and rel proteins:: Evolutionarily conserved mediators of immune responses [J].
Ghosh, S ;
May, MJ ;
Kopp, EB .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :225-260
[9]   Induction of the pro-inflammatory NF-kB-sensitive miRNA-146a by human neurotrophic viruses [J].
Hill, James M. ;
Clement, Christian ;
Zhao, Yuhai ;
Lukiw, Walter J. .
FRONTIERS IN MICROBIOLOGY, 2015, 6
[10]   Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type I interferon [J].
Ho, Bing-Ching ;
Yu, I-Shing ;
Lu, Li-Fan ;
Rudensky, Alexander ;
Chen, Hsuan-Yu ;
Tsai, Chang-Wu ;
Chang, Yih-Leong ;
Wu, Chen-Tu ;
Chang, Luan-Yin ;
Shih, Shin-Ru ;
Lin, Shu-Wha ;
Lee, Chun-Nan ;
Yang, Pan-Chyr ;
Yu, Sung-Liang .
NATURE COMMUNICATIONS, 2014, 5